title: Preclinical evaluation of biopolymer-delivered circulating angiogenic cells in a swine model of hibernating myocardium.
abstract: BACKGROUND
  Vasculogenic cell-based therapy combined with tissue engineering is a promising revascularization approach targeted at patients with advanced coronary artery disease, many of whom exhibit myocardial hibernation. However, to date, no experimental data have been available in this context; we therefore examined the biopolymer-supported delivery of circulating angiogenic cells using a clinically relevant swine model of hibernating myocardium.
  
  
  RESULTS
  Twenty-five swine underwent placement of an ameroid constrictor on the left circumflex artery. After 2 weeks, animals underwent echocardiography, rest and stress ammonia-positron emission tomography perfusion, and fluorodeoxyglucose positron emission tomography viability scans. The following week, swine were randomized to receive intramyocardial injections of PBS control (n=10), circulating angiogenic cells (n=8), or circulating angiogenic cells+collagen-based matrix (n=7). The imaging protocol was repeated after 7 weeks. Baseline positron emission tomography myocardial blood flow and myocardial flow reserve were reduced in the left circumflex artery territory (both P<0.001), and hibernation (mismatch) was observed. At follow-up, stress myocardial blood flow had increased (P≤0.01) and hibernation decreased (P<0.01) in the cells+matrix group only. Microsphere-measured myocardial blood flow validated the perfusion results. Arteriole density and wall motion abnormalities improved in the cells+matrix group. There was also a strong trend toward an improvement in ejection fraction (P=0.07).
  
  
  CONCLUSIONS
  In this preclinical swine model of ischemic and hibernating myocardium, the combined delivery of circulating angiogenic cells and a collagen-based matrix restored perfusion, reduced hibernation, and improved myocardial wall motion.
authors.affiliation: Division of Cardiac Surgery, Molecular Function and Imaging Program at the Cardiac PET Centre, Division of Cardiology, and Department of Cellular and Molecular Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Céline
authors.initials: C
authors.lastname: Giordano
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Thorn
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Renaud
authors.forename: Talal
authors.initials: T
authors.lastname: Al-Atassi
authors.forename: Munir
authors.initials: M
authors.lastname: Boodhwani
authors.forename: Ran
authors.initials: R
authors.lastname: Klein
authors.forename: Drew
authors.initials: D
authors.lastname: Kuraitis
authors.forename: Girish
authors.initials: G
authors.lastname: Dwivedi
authors.forename: Pingchuan
authors.initials: P
authors.lastname: Zhang
authors.forename: Jean N
authors.initials: JN
authors.lastname: Dasilva
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Ascah
authors.forename: Robert A
authors.initials: RA
authors.lastname: Dekemp
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Suuronen
authors.forename: Rob S B
authors.initials: RS
authors.lastname: Beanlands
authors.forename: Marc
authors.initials: M
authors.lastname: Ruel
mesh_terms: D000818:Animals; D001704:Biopolymers; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D055252:Cell-Derived Microparticles; D002478:Cells, Cultured; D003326:Coronary Circulation / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D017682:Myocardial Stunning / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D013552:Swine; D013556:Swine, Miniature; D016896:Treatment Outcome; D016277:Ventricular Function, Left
chemical_list: D001704:Biopolymers
keywords: cell transplantation; hibernation; positron-emission tomography; tissue engineering